INTRODUCTION: Oral squamous cell carcinoma (OSCC) accounts for more than 90% of all oral cancers with high mortality and morbidity rates. Lymph node (LN) metastasis is one of the most important factors in the treatment and prognosis of patients with OSCC. It reduces the overall survival by nearly half. Toll like receptors (TLRs) are evolutionarily conserved proteins and major type of receptors involved in both innate and adaptive immunities and defense against pathogens. TLR4 was the first member of the TLR family to be discovered. It was verified that TLR4 is expressed in many types of tumors including OSCC. The correlation between the expression of this receptor and the presence of nodal metastasis has been studied. Involvement of TLR4 in the invasion and metastasis potentials may thus suggest the use of this protein as a prognostic marker for OSCC and may provide a new insight in the treatment strategy. OBJECTIVES: The aim of the present study was to assess the expression of TLR4 in the primary tumor of OSCC and correlate it with the lymph node status. MATERIALS AND METHODS: TLR4 expression was calculated in 30 OSCC cases. The specimens were taken from the primary tumor of 15 cases proved to have positive lymph nodes and another 15 cases with negative lymph nodes. Immunohistochemical (IHC) staining was performed using the Labeled Strept-Avidin Biotin complex method (LSAB), using the anti-TLR4 antibody. RESULTS: TLR4 was expressed in the OSCC cases and was significantly higher in cases with positive lymph node metastasis than those without. CONCLUSIONS: TLR4 expression could be used as a prognostic marker for OSCC as an indicator for metastasis.